Suvorexant and mirtazapine improve chronic pain-related changes in parameters of sleep and voluntary physical performance in mice with sciatic nerve ligation

Ito, Hisakatsu; Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Toyooka, Naoki; Matsuo, Mitsuhiro; Yamazaki, Mitsuaki

doi:10.1371/journal.pone.0264386

Cited by 8 publications

(4 citation statements)

References 48 publications

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“…Wakefulness was reduced and fragmented, indicating that CCI mice are unable to maintain wakefulness in a normal manner. Our observations were consistent with previously reported sleep disturbance in NP mice (Ito et al, 2022) and the critical roles of the P2X7R in sleep disturbance induced by NP (Krueger et al, 2010). Notably, the administration of P2X7R inhibitor could effectively recover the activation of microglia in cortex, the decrease of NREM sleep and the increase of wakefulness in CCI mice during the 24-h cycle.…”

Section: Discussionsupporting

confidence: 93%

P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain

Gao²,

He³

et al. 2023

Front. Neurosci.

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Neuropathic pain (NP) is associated with sleep disturbances, which may substantially influence the quality of life. Clinical and animal studies demonstrated that neurotransmitter is one of the main contributors to cause sleep disturbances induced by NP. Recently, it was reported that P2X7 receptors (P2X7R) are widely expressed in microglia, which serves crucial role in neuronal activity in the pain and sleep-awake cycle. In this study, we adopted the chronic constriction injury (CCI) model to establish the progress of chronic pain and investigated whether P2X7R of microglia in cortex played a critical role in sleep disturbance induced by NP. At electroencephalogram (EEG) level, sleep disturbance was observed in mice treated with CCI as they exhibited mechanical and thermal hypersensitivity, and inhibition of P2X7R ameliorated these changes. We showed a dramatic high level of P2X7R and Iba-1 co-expression in the cortical region, and the inhibition of P2X7R also adversely affected it. Furthermore, the power of LFPs in ventral posterior nucleus (VP) and primary somatosensory cortex (S1) which changed in the CCI group was adverse after the inhibition of P2X7R. Furthermore, inhibition of P2X7R also decreased the VP-S1 coherence which increased in CCI group. Nuclear magnetic resonance demonstrated inhibition of P2X7R decreased glutamate (Glu) levels in thalamic and cortical regions which were significantly increased in the CCI mice. Our findings provide evidence that NP has a critical effect on neuronal activity linked to sleep and may built up a new target for the development of sleep disturbances under chronic pain conditions.

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Section: Discussionsupporting

confidence: 93%

P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain

Gao²,

He³

et al. 2023

Front. Neurosci.

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“…The power density of delta waves during NREM sleep is closely associated with sleep depth. 28 , 32 , 33 As expected, mice exhibited increased delta-wave power density during baseline NREM sleep in both the dark and light phases ( Supplementary Fig. 3G and H ), which was not affected by acute NTG treatment ( Supplementary Fig.…”

Section: Resultssupporting

confidence: 70%

Unraveling the directional relationship of sleep and migraine-like pain

Lillo Vizin,

Kopruszinski,

Redman

et al. 2024

Brain Communications

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Migraine and sleep disorders are common comorbidities. Patients frequently link their sleep to migraine attacks suggesting a potential causal relationship between these conditions. However, whether migraine pain promotes or disrupts sleep or whether sleep disruption can increase the risk of migraine remains unknown. We assessed the potential impact of periorbital allodynia, a measure consistent with migraine-like pain, from multiple preclinical models on sleep quantity and quality. Additionally, we evaluated the possible consequences of sleep deprivation in promoting susceptibility to migraine-like pain. Following implantation of EEG/EMG electrodes to record sleep, mice were treated with either single or repeated systemic injections of nitroglycerin at the onset of their active phase (i.e., nocturnal awake period). Neither single nor repeated nitroglycerin affected total sleep time, non-rapid eye movement sleep, rapid-eye movement sleep, sleep depth, or other measures of sleep architecture. To account for the possible disruptive effects of the surgical implantation of EEG/EMG electrodes, we used immobility recordings as a non-invasive method for assessing sleep-wake behavior. Neither single nor repeated nitroglycerin administration during either the mouse sleep (i.e., daylight) or active (i.e., night) periods influenced immobility-defined sleep time. Administration of an inflammatory mediator mixture onto the dura mater at either sleep or active phases also did not affect immobility-defined sleep time. Additionally, inhalational umbellulone-induced migraine-like pain in restraint-stressed primed mice did not alter immobility-defined sleep time. The possible influence of sleep disruption on susceptibility to migraine-like pain was evaluated by depriving female mice of sleep over 6 h with novel objects, a method that does not increase circulating stress hormones. Migraine-like pain was not observed following acute sleep deprivation. However, in sleep-deprived mice, subthreshold doses of systemic nitroglycerin or dural calcitonin gene-related peptide induced periorbital cutaneous allodynia consistent with migraine-like pain. Our data reveal that while migraine-like pain does not significantly disrupt sleep, sleep disruption increases vulnerability to migraine-like pain suggesting that a therapeutic strategy focused on improving sleep may diminish migraine attacks.

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“…Activity recording. Mice were individually placed in plastic cages with a rotating exercise wheel (Melquest, Toyama, Japan) 66 . A revolution sensor was installed in the exercise wheel to detect spontaneous movements of the animals.…”

Section: Methodsmentioning

confidence: 99%

Glucocorticoids coordinate the bladder peripheral clock and diurnal micturition pattern in mice

et al. 2023

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Peripheral clocks function to regulate each organ and are synchronized though various molecular and behavioral signals. However, signals that entrain the bladder clock remain elusive. Here, we show that glucocorticoids are a key cue for the bladder clock in vitro and in vivo. A pBmal1-dLuc human urothelial cell-line showed significant shifts in gene expression after cortisol treatment. In vivo, rhythmic bladder clock gene expression was unchanged by bilateral adrenalectomy but shifted 4 h forward by corticosterone administration at the inactive phase. Moreover, the bladder clock shifted 8–12 h in mice that underwent both bilateral adrenalectomy and corticosterone administration at the inactive phase. These mice showed decreases in the diurnal rhythm of volume voided per micturition, while maintaining diurnal activity rhythms. These results indicate that the diurnal rhythm of glucocorticoid signaling is a zeitgeber that overcomes other bladder clock entrainment factors and coordinates the diurnal rhythm of volume voided per micturition.

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Suvorexant and mirtazapine improve chronic pain-related changes in parameters of sleep and voluntary physical performance in mice with sciatic nerve ligation

Cited by 8 publications

References 48 publications

P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain

P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain

Unraveling the directional relationship of sleep and migraine-like pain

Glucocorticoids coordinate the bladder peripheral clock and diurnal micturition pattern in mice

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